Methods for cell-type specific profiling to identify drug targets

A method of profiling the gene expression of a human, mouse, or rat nucleus, the method comprising:

• (a) processing a human, mouse, or rat tissue sample containing a plurality of cell types to expose nuclei, wherein the tissue sample comprises brain tissue, brain stem tissue, and/or spinal cord tissue;
• (b) permeabilizing, and then labeling at least one nucleus of the nuclei from the processed tissue sample by contacting the nuclei from the processed tissue sample with two or more affinity labels, wherein each of the two or more affinity labels binds a different nucleic acid transcript or protein of the nucleus of at least one cell type of the plurality of cell types contained in the tissue sample, wherein the different nucleic acid transcript or protein is encoded by a gene selected from the group consisting of:
• Cadps2, Reln, Synpr, Galnt5, Ccm21, Srrm4, Tmem266, Cckbr, Cerkl, Chn2, Grik2, Mal2, Fat2, Adamts16, Len8, Fst15, T11, Vsnl1, Rit2, Slc8a2, Slc17a7, Zp2, Tspan18, Fgf5, Pragl, Slc6a7, Rims1, Cdh7, Licam, Mical2, Ptk2b, Kcnhl, Arhgap29, Cdk15, Pde3b, Itga4, Etv1, Tmem178, Chgb, Coll3al, Rnf152, Kenk1, I116, Sstr2, Als2, Barhl1, Scn2a, CbIn1, Dusp5, Ndst3, Lurap11, Kenj 12, Snai2, Ifnlrl, Neurod1, Cdyl2, Pppiric, Jkamp, Neurlla, Trhde, Mfsd9, Xkr7, Barhl2, CbIn3, Uncx, Ptchd1, Cblb, Runx1t1, Sphkap, Gabra6, Coro2a, Bmper, Dkk4, Camk4, Uncl3c, Trp53i11, Ephb1, Glb113, Mdgal, Kencl, Tmem252, Mpp7, Hipk4, Tmem51, Cacnb3, Cyb5a, Tmem?2, 6430573f1 Lrik, Rasgrp1, Rab37, Adarb1, Svop, Pgm5, Mthfd11, Cdh15, Vwe2, Disp2, Tspan15, Sle26a5, Lhfp, Arhgef33, Car8, Slcla6, Calb1, Ppplr17, Itpr11, Zfp385c, Ryrl, Aabr07030473.1, Slc9a3, Aabr070067 13.1, Aabr070067 13.2, Red1561557, Gpr63, Aabr07049491.1, Aabr07006727.1, Plxdcl, Cep76, Fam 107b, B3gnt5, Far2, Ac108261.1, Grid2ip, Aabr07072628.1, Kcnip1, Aabr07006724.1, Trpc3, Phka2, Car7, Fam117a, Hes3, Casq2, Dekh, Arhgap26, Trabd2b, Nelll, Bell la, Coll8al, Loc 100125362, Ptchd4, Camk2a, Dyrk4, Kitlg, Kcnab1, Nxnl2, Ltk, Loc689927, Aabr07056156.1, Cpne8, Htrlb, Aabr07033570.1, Icmt, Aabr07047598.1, Cstf2t, Grik1, Itpka, Loc 100910996, Hpcall, Efna5, Myol10, Rgs8, Skor2, 1122, Slc12a3, Cpne9, Aabr07007980.2, Cacnalg, Doc2b, Sptbn2, Loc108351705, Aabr07035926.1, Aabr07037943.1, Pep2, Aabr07061860.1, Aabr07024820.1, Impg1, Nkiras2, Krtap 12-2, Tmem 123, Aabr07044009.1, Ptprr, Homer3, Garn13, Sos1, Cntn3, Loc304725, Stk17b, Aabr07047604.1, Zdhhc23, Scn4b, Ac126640.1, PdeYa, Ptprb, Prkcg, Pcp4, Aabr07056374.1, Fst14, Ppp4r4, Nup93, Bhlhe22, March11, Kit, Tfap2b, Clmp, Lbx1, Slc38a5, Frmd3, Btbd11, Lipg, Rab3b, Lrrc38, Galnt14, Cnrl, Tcerg 11, CbIn2, Siah3, Stac2, Scgn, Rspol, Lmcd1, Lpl, Adralb, Gad2, Chrna3, Socs2, Trpc6, Kcena3, Syn3, Em115, Nefl, Fam84a, Trpc5, Kiaal644, Hrh3, Disp3, Tfap2a, Gjd2, Adamts2, Sorcs3, Ptprk, Timp3, Gjb4, Ehd3, Cxcl12, Actcl, Pnma2, Fam43a, Adam11, Dact2, Rgs16, Slc5a8, Exph5, Cfap221, Myol6, Megf10, Cacnald, Pax2, Plch1, Gabrg2, Prrt4, Itga5, Sp5, Nefm, Grik3, Cx3cl1, Fbxo024, Lect2, Nefh, Efnb3, Grk3, Mpz, Syt2, Scrtl, Cdc42ep3, Trim67, Grin2b, Rab3c, Plxna4, Fzd8, Elmod1, Smim17, Slc8a3, Nrip3, Plekhg5, Arl4a, Grm8, Cntnap5a, Maats1, Lox12, Arap3, Dcx, Nyap2, Skor1, Pvalb, Ppm1j, Slc5a4a, Tmem132e, Cygb, Slprl, Gjal, Lgi4, Efemp1, Etnppl, Aqp4, Regma, Lgr6, Lcat, Tril, Serpini2, Pgghg, Slcla3, Gfap, Aldhlal, Pla2gc5, Fxyd1, Wdr49, Glil, Nfatc4, Scara3, Sle4a4, Lama2, Cdc42ep4, Gabrg3, P2ryl, Gabra2, Colec12, Mlc1, Slc7al1, Aldh111, Sox9, Lgals3, Mgstl, Gats13, Ahnak, Pipox, Rhoj, Arhgef26, Arhgef28, Srpx, Mt3, Atpla2, Fxyd7, Lfng, Lamb2, Gdf10, F3, Sdc4, Hspb1, Hes1, Slc12a4, Mertk, C3, Ai464131, Id4, Vit, Fjx1, Ccdc80, Adora2b, Ryr3, Mfge8, Plekho2, Elov12, Fam179a, Cebpb, Acss1, Slc13a5, Ednrb, Pltp, 1133, Tlr4, Fam198b, Isynal, Glis3, Dao, Fefr3, Ncan, Msx2, Spatcl, Pdgfrb, Tubb2b, Fat3, Fam167a, Col22al, Tcf711, Ndrg2, Nhsl1, Ddit41, Pbxip1, Ras112, Sh3bp2, AplInr, Robo3, Rubcnl, Rab34, Gtf2all, Fefr2, Kank2, Rfx4, Klk6, Mog, Gldn, Cndp1, Gm20425, Tmem98, Sle5al1, Mag, Carns1, Gpr37, Cdk18, Hhatl, AnIn, Enpp2, Folhl, Sec1415, Myrf, Plp1, Mal, Gjb1, Itga2, Cpm, Plpp2, Cntn2, Ermn, Opalin, Abca8b, Lpar1, Pld1, Salll, Cercam, Dock5, Pil6, Man2al1, Pex51, Tmem63a, Tmem125, Gipr, Sh3tc2, D7ertd443e, Kel, Ldb3, Cedc152, Cldn11, Synj2, Lrp2, Ninj2, Psrcl, Ndrg1, Actn2, Sgk2, Trim59, Plekhg3, Larp6, Slc45a3, Cnp, Col4a5, Pde8a, Rhobtb1, D16ertd472e, Qdpr, Enpp6, Rhou, Sema3c, Gsn, Cyr61, Capn3, Hoxd1, Frmd4b, Tmem144, Galnt6, Pkmyt1, Fbxo32, Pla2g16, Dpyd, Sh3g13, Primal, Rasall, Fa2h, Fam124a, Treh, Paqr4, Azgp1, Plekhh1, Dapk2, Knop1, Sema3b, Elovll, Shroom4, Car2, Necabl, Aspa, Gab1, Kif6, Hhip, Ugt8a, Iqgap1, Map6d1, Eln, Pllp, Fermt1, Lims2, Clql1, Sstr1, Olig1, Bambi, Usp43, B3gnt7, Pdgfra, Cl1q12, Olig2, Fmo3, Cspg5, Galrl, Gpc2, Fibin, Cspg4, Colllal, Bche, Col9al, Afap112, Cldn1, Plpp4, Sox13, Plat, Neu4, D630023f18rik, Col20al, Pxylp1, Asic4, Spsb4, Prelp, Gpr34, Best3, Stk32b, Akrlc14, Susd5, Ophnl, Mmp16, Sulf2, Prkg2, Tns3, B3galt4, Fefbp3, Nkain3, Ntnl, Ascll, Sema5a, Hrasls, Gal3st4, Ebf4, Tmem 132d, Nt5e, Jagl, Megf11, Ildr2, Plppr1, Dec, Ntn4, Sox6, Cacng4, Pxdn, Sapcd2, Tnk2, Slc43a3, Adamts6, Vsig8, Itm2a, Marcks11, Alk, Smocl, Cacna2d3, Tm4sf1, Bgn, Pdgfc, Atp2c2, Aldhla3, Prrx1, Meis3, Cxxc4, Cd27, Sema3e, Adamts17, Akrlc20, Arhgap10, Crispld2, Sipall2, Ppplr36, Gng12, Syt17, Midn, Gadd45a, Khdrbs3, Thbs4, Vipr2, Ccnd1, Iffol, Atoh8, Exosc4, Pde7b, Tesc, Itga7, Rbfox3, Aabr07013140.1, Calb2, Aabr07030880.1, Prrt2, Gabrd, Aabr07026032.2, Sv2b, Car4, Nrep, Aabr07043098.3, Rtn4r, Shisa8, Sel113, Grb7, Rg13, Lamp5S, Pagr1, Cemip, Gpre5Sc, Shf, Wdr66, Tmem44, Pax6, Capn1, Calhm3, Aabr07043098.1, Selm, Sema3g, Loc100360491, Diras2, Agb112, Mctp1, Mvp, Plk5, Mrgprf, Loc100910401, Ak4, Wscd2, Grin2a, Cfap74, Rnf39, Fzd7, Golga7b, Aabr07033679.1, Ptpn22, Grin2c, Ablim1, Arpp21, Clrl, Zscan30, Maf, Rtn4rl1, Kenk12, Actl6b, Aabr07053850.1, Sdcl, Camkk2, Nuded3, Cedc155, Cbfa2t3, Aabr07037151.1, Jph3, Itgal1, Rnf182, Rgd1560784, Plcxd3, Ablim3, Nyx, Aabr07034445.1, Aabr07025051.3, Kenk10, Kcnk3, Nol3, Atp2a3, Clic6, Plekhd1, Sycpl, Pde5a, Tspan11, Pet100, Strip2, Dagla, Gng13, Rnf207, Arhgap20, Grip1, Cck, Ebf1, Beanl, Tuba8, Smpx, Ebf2, Slc19al, Ccdc85a, Flt3, Sh2d4b, Clec21, Hrh2, Ksr2, Chtf18, Vax2, Foxp4, Ankrd33b, Corin, Prkag3, Cep126, Slc20a1, Akain1, Nrk, Pihlh3b, Inpp5a, Lhx1, Paxbp1, Dner, Tspoap1, Gfra2, Fh15, Dmd, Kenab2, Serinc2, Dnah6, Prmt8, Mdfi, Nek2, Fmnl1, At12, Cfap161, Lin28b, Cacna2d2, Pkp3, Shank1, Grid2, Aabr07001734.1, Lypd6, Lama3, Gldc, Aabr07047823.1, Aabr07001623.1, Aabr07070578.1, Hpcal4, Aabr07061428.1, Coll2al, Enpp1, Plk2, Rgd1561667, Asic2, Aabr07026472.1, Ac124896.1, Aabr07052084.1, Aabr07059478.1, Nt5dc2, Aabr07041885.1, Henl, Prdm8, Phf24, Esrrg, Mir346, Tmem200a, Aabr07003600.7, Scn9a, Inpp4b, Ace, Kcna2, Adrald, Sle32al, Cntnap4, Gridl, Trpe7, Begain, Aabr07049535.3, Frmpd4, Aabr07054088.3, Zcchc16, Trpv6, Grb10, Nrxn3, Tyms, Myt11, Aabr07063359.1, Btnlal, Rn60_10_0565.6, Aabr07041972.1, Osbp110, Six4, Mir384, Tbc1d4, Cabp1, Aabr07003600.2, Aabr07057590.1, Adrb2, Plxncl, Dusp22, Hecw1, Gdpd4, Rno-Mir-344a-1, Lgi2, Aabr07060291.2, Adarb2, Angptl, Rspo4, Rn50_7_1158.3, Aabr07065531.31, Onecutl, Mkx, Rgs4, Kcnce2, Hef, Fef13, Itga8, AabrO7070578.2, Apcdd1, Trim15, Aabr07070161.1, Itih3, Slc25a18, Nkain4, Tne, Slc7a10, Aqp9, Mt2a, Pou3f2, Cacng5, Cyp2d5, Aabr07058658.1, Aabr07070161.6, Aabr07070161.3, Fam107a, Nat8f3, Ctxn3, Entpd2, Rbm24, Cxcll4, Hif3a, Acsbg1, Aabr07070161.7, Notch3, Nwd1, Samd91, Gabrb1, Plpp3, Cxcr4, Pdlim4, Sgca, Sncaip, Prodh1, Agt, Slcl4al, Aabr07032343.1, Aabr07035782.1, Marc1, Aabr07070161.5, Ac109886.1, Prr5, Aabr07035780.2, Sh2b2, Sparcll, Evala, Cyp2d4, Crif1, Sod3, Chst1, Aabr07001555.1, Aabr07063346.1, Mpp6, Ptch2, Aabr07031767.1, Ac105604.1, Pygm, Slc15a2, Casp4, Grial, Camk2g, Cbs, Aabr07035175.1, Ntsr2, Aspg, Sfxn5, Ccbel, Gramd3, Shroom3, Myh11, Mobp, Aabr07006310.1, HapIn2, Selplg, Aabr07046961.1, Abi3, Tmem88b, Rasgrp3, Prr51, Loc 100362909, Tmem176b, Loc100302465, Cx3crl, Ctss, Tmem176a, Tf, Cl qb, Apod, Slpr5, Rn60_5_1374.5, Insc, Mbp, Pls1, Pafahlb1, Loc361016, Trim36, Aabr07017693.1, Gpatch4, Hamp, Csflr, Gjc2, Car14, Aabr07053870.1, Gpr84, Ghr, Kndcl, Slco2b1, Cd74, Trpv3, Aabr07008030.1, Aplp1, Tgfbr2, Ptp4a3, Pik3c2b, Aabr07036035.1, Pld4, Fam102b, Cd33, Cdknla, Nkd1, Elov17, Piga, Inf2, Blnk, Enpp4, 1118, Spatal3, Mettl7a, Inpp5d, Gyjc3, Trim2, Aabr07012039.1, Aabr07033887.1, Pacs2, Clqa, Trem2, Anxa3, Aabr07022098.1, Fam89a, Rgd1561849, Rlbp1, Tmem255b, Itga9, Ppfibp1, Snx22, Col5a3, Pmel, Cav 1, Serpine2, Aabr07052897.1, Cdk2, Aabr07010022.1, Matn4, Aabr07049948.1, Pxdel, Rgd1566029, Aabr07003304.1, Mmp15, Rgcc, Slc22a6, Sema5b, Qprt, Pnlip, Slc6al2, Rgd1311892, Aabr07003306.1, Aabr07044671.1, Rbpjl, Chst5, Traf4, Cox6b2, Pedh15, Cd101, Xylt1, Aabr07003304.2, Calcrl, Collal, Lama4, Elfnl, Ampd3, Fam212b, Slc6al3, Sema3d, Ac141997.1, Cpne7, Ptgfrn, Wbscr28, Gpsm2, Netol, Chst11, Slc22a8, Pstpip2, Aabr07044668.1, Bcas1, Igf2, Lbh, Olfm2, Ndnf, Vstm2b, Aabr07058656.1, Rep15, Vtn, Ramp1, Pmepal, Gpnmb, Ptpro, Limd1, Cdh13, Nrxn2, Mgp, Mytl, Marcks, Loc 100362216, Aabr07043601.4, Loc 102553018, Masp1, Tle6, Fam114al, Tmem100, Ccnd2, Rasgef1b, Ppfia4, Sidtl, Rims3, Olfm3, Des, Svep1, Cacna2d1, Cacnale, Patj, Atp2b3, Marveld2, Rab15, Rapgef4, Lin7a, Igfbp5, Vatll, Msra, Rps6kal, Ryr2, Kif26b, Adamts 18, Mmp24, Cdh8, Cadm3, Ntf3, Pld5, Syndig11, Galnt15, Sh2dla, Panx2, Speg, Bsn, Rnf112, 120rb, Slc16a10, Adcyl, Mapk12, Boc, Syt12, Tead4, Clen1, Pgm211, Tmtc4, Abcc8, Olfm1, Nedd41, Lurap1, Krt24, Adamts15, Penk, Galnt18, Asgrl, Chst9, Flrt2, Chacl, Pla2g4e, Camklg, Stc2, Lamb1, Coro6, Kirrel, Cdkl1, Asns, Cryba2, Aldh112, Kcnab3, Tg, Prkcd, Cgn, Tctel, Serpinil, Slce7al, Gpr22, Cntn4, Slce7a3, Atplb1, Parm1, Dock7, Cnih3, Mtfp1, Ret, Zfp423, NIn, Neurod6, Grin2d, Angpt13, Rasgrfl, Scnnlg, Ly6e, Rph3a, Rai2, Igsf3, Tmem179, Sorbs2, A2m, Mybpcl, Slco4al, Fam20a, Acotl1, Vim, Prex2, Cables1, Pla2g¢7, Phkg1, Gjb6, Plcel, Pax3, Gpr153, Abi3bp, Rpusd3, Igdcec3, Ucp2, Frem1, Gli2, Efhd2, Zic4, Oplah, Atp13a4, Trafl, Dmp1, Gabra4, Etv4, Map2k6, Wwel, Syt110, Sparc, Mxra8, Egfr, Slc39a12, Slce8b1, Glipr2, Axl, Aass, Hk2, Itpkb, Ramp2, Pyroxd2, Garem2, Wnt6, Dfna5, Fam92b, Plxnb11, Vamp1, Tnfaip6, Fthl, Pkd211, Kenk13, Ppp1r14a, Gatm, Serpinbla, Tnnil, Glul, Tmprss5, Nipal4, Slc12a2, Litaf, Edil3, Mboat1, St6galnac3, Gng11, Myold, 4933413¢19rik, Pigh, Map7, Depdc7, Aatk, Stmn4, Chdh, Nek4, Palm2, Arsg, Rftn1, Itgb4, Emilin2, Nkain2, Adamts14, Hen2, Plxnb3, Dpy1911, Arhgap23, Tubb4a, Kcetd13, 3110035e14rik, Tes, Rprm, Amz], 181004 1115rik, Tox3, Sh3bp4, Galnt3, Grm5, Mmp2, Coll 1la2, Ren1, 5730559c 18rik, Lpcat2, Fh13, Tspan6, Rin2, Basp1, Fzd9, Abhd2, Ctxn1, Cfap20, Cdol, Gsx1, Sertm1, Slclal, Matnl, Has2, Mycl, Klh15, Kcenh5, Kcenh8, Slc5a7, Cav2, Adm, Adam12, $100a4, Mfsd2a, Igfbp3, Asap3, Abcg2, Dock6, Fbn1, Frrs1, Slitrk6, Ptpn14, Dpys13, Slc44a5, Eyal, Phox2a, Swap70, Mrm2, Lypd1, Shisa7, and Pcdh17, wherein the affinity labels are selected from the group consisting of an antibody, a RNA probe, and a DNA probe;
• (c) purifying the at least one labeled nucleus using the affinity labels on the at least one labeled nucleus;
• and
• (d) measuring expression of one or more nucleic acid transcripts and/or proteins in the at least one labeled nucleus, thereby profiling the gene expression of the nucleus.